gentamicin (Rx)

Susceptible Infections

In underweight and nonobese patients, use of total body weight (TBW) instead of ideal body weight for determining initial mg/kg/dose is accepted; ideal body weight (IBW) also may be used to determine doses for patients who are neither underweight nor obese

Conventional dosing

• 3-5 mg/kg/day IV/IM divided q8hr  

Extended dosing interval

• Initial: 5-7 mg/kg/dose IV qDay  
• Not for use in patients with ascites, burns covering >20% of total body surface area, cystic fibrosis, end-stage renal disease, endocarditis, infants, mycobacterial infections, or pregnancy
• Measure gentamicin level between 6 and 14 hr after initiating gentamicin infusion; use institution-specific nomogram to determine appropriate dosing interval

Surgical Prophylaxis (Off-label)

5 mg/kg IV as single dose 1 hr prior to surgical incision; alternativley, 1.5 mg/kg IV as single dose for gynecology procedures  

Dose is based on actual body weight (TBW) unless body weight is >20% above ideal body weight (IBW), in which case the dosing weight can be estimated by IBW + 0.4 (TBW - IBW)

Infective Endocarditis Treatment

Enterococcus (native or prosthetic valve); Off-label dose

• 3 mg/kg/day IV/IM divided q8hr for 4-6 weeks in combination with a beta-lactam and for 6 weeks when administered wiht vancomycin  
• Organism sensitivity testing should determine choice of concomitant antiibotic and treatment duration

S. aureus (prosthetic valve; methicillin susceptible or resistant); Off-label dose

• 3 mg/kg/day IV/IM divided q8-12hr for 3-5 days for native valve infections or for 2 weeks for prosthetic valve infections in combination with other antibiotic  
• Organism sensitivity testing should determine choice of concomitant antibiotic

Viridans group streptococcus and S bovis (native or prosthetic valve); Off-label use

• 3 mg/kg/day IV/IM qDay (preferred) or divided q8hr for 2 weeks for native or prosthetic valve infections or for 6 weeks for prosthetic valve infections with relatively or fully resistant strains in combination with other antibiotic  
• Organism sensitivity testing and source of infection should determine choice of concomitant antibiotic

Cystic Fibrosis (Off-label)

7.5-10.5 mg/kg/day IV/IM divided q8hr  

Pelvic Inflammatory Disease (Off-label)

Loading dose: 2 mg/kg IV or IM  

Maintenance dose: 1.5 mg/kg IV/IM q8hr plus clindamycin IV or 3-5 mg/kg IV qDay

May initiate transition from parenteral to oral therapy of either oral doxycycline or oral clindamycin within 24-48 hr of clinical improvement for total treatment duration of 14 days

Plague (Yersinia pestis) Treatment (Off-label)

5 mg/kg IV/IM qDay for 10 days or 2 mg/kg IV/IM loading dose; then 1.7 mg/kg/dose IV/IM q8hr for 10-14 days or until 2 days after patient is afebrile; doxycycline, ciprofloxacin, or chloramphenicol could be used as third-line alternatives  

Dosage Modifications

Renal impairment

• Conventional dosing

  • Renally adjusted dose recomendations are based on doses of 1.7 mg/kg/dose q8hr or 5-7 mg/kg/dose once daily  
  • CrCl>50 mL/min: No dosage adjustment necessary
  • CrCl 10-50 mL/min: Administer q12-48 hr
  • CrCl<10 mL/min: Administer q48-72 hr

• Once daily (interval adjustment of extended interval dosing)

  • Adjust doses based on serum concentrations and organism MIC
  • CrCl≥60mL/min: No dosage adjustment necessary
  • CrCl 40-59 mL/min: 5-7 mg/kg IV q36hr  
  • CrCl 20-39 mL/min: 5-7 mg/kg IV q48hr
  • CrCl<20 mL/min: 5-7 mg/kg IV once; monitor serum levels and redose when gentamicin level is <1 mcg/mL

• Intermittent hemodialysis

  • Administer after hemodialysis on dialysis days
  • Dependent on patients size, site of injection, filter, duration and type of intermittent hemodialysis, it is ~30-50% dialyzable
  • 1-1.7 mg/kg IV/IM after initial hemodialysis session; serum gentamicin concentrations should guide subsequent dosing  
  • Dosing dependent on assumption of 3 times/wk complete intermittent hemodialysis sessions

• Peritoneal dialysis

  • Intermittent dosing: 0.6 mg/kg per exchange once daily for anuric patients; 0.75 mg/kg/dose IP for non-anuric patients qDay during long dwell periods; depending on infecting organism and patient's clinical status, may treat for 2-3 weeks  
  • Continuous dosing: 8 mg/L loading dose; followed by 4 mg/L maintenance dose

• Continuous renal replacement therapy

  • Drug clearance is highly dependent on method of renal replacement, filter type, and flow rate; close monitoring of pharmacologic response, sign of adverse reactions due to accumulation, and target drug concentration necessary for appropriate dosing
  • 3 mg/kg/day IV/IM divided q8hr; may administer up to 5 mg/kg/day IV/IM divided q6-8hr in life-threatening infections; peak; adjust dose based on serum concentration monitoring; peak concentration >12 mcg/mL should be avoided  

Dosing Considerations

Gentamicin may be administered IV/IM

Infuse over 30-120 min when administering IV

Dosing regimens are numerous and are adjusted based on CrCl and changes in volume of distribution, as well as on the body space where distribution of the agent will occur

Monitor peak (4-12 mg/L) and trough (1-2 mg/L)

Monitor nephrotoxicity, neurotoxicity, and ototoxicity; assess at beginning of therapy and throughout

Each regimen must be followed by at least trough level drawn on third or fourth dose, 30 min before dosing unless renal toxicity suspected

May draw peak level 30 min after 30-min infusion has been completed or 1 hr after IM injection

Use ideal body weight for mg/kg/dose; more accurate than total body weight

Gentamicin is usually a first-line aminoglycoside against infections with gram-negative organisms such as Pseudomonas aeruginosa, Proteus, Escherichia coli, Klebsiella, Enterobacter, Serratia, and Citrobacter, as well as against Staphylococcus (gram- positive)

Bacterial organisms causing susceptible infections

• Susceptible infections include the following:
• Pseudomonas aeruginosa
• Proteus species (indole-positive and indole-negative)
• Escherichia coli
• Klebsiella-Enterobacter-Serratia species
• Citrobacter species
• Staphylococcus species (coagulase-positive and coagulase-negative)
• Pseudomonas aeruginosa
• Proteus species (indole-positive and indole-negative)
• Escherichia coli
• Klebsiella-Enterobacter-Serratia species
• Citrobacter species
• Staphylococcus species (coagulase-positive and coagulase-negative)

Mycobacterium Infection (Orphan)

Gentamicin liposome injection: For disseminated Mycobacterium avium-intracellulare infection

Orphan indication sponsor

• Liposome Company, Inc; One Research Way; Princeton, NJ 08540

Susceptible Infections

Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than on the basis of total body weight (TBW)

Infants: 2.5 mg/kg/dose IV/IM q8hr

Children and adolescents:: 2-2.5 mg/kg/dose IV/IM q8hr  

<30 weeks' gestation

• 0-28 days: 2.5 mg/kg/day IV/IM  
• >28 days: 3 mg/kg/day IV/IM

30-36 weeks' gestation

• 0-14 days: 3 mg/kg/day IV/IM  
• >14 days: 5 mg/kg/day IV/IM divided q12hr

>36 weeks' gestation

• 0-7 days: 5 mg/kg/day IV/IM divided q12hr  
• >7 days: 7.5 mg/kg/day IV/IM divided q8hr

Surgical Prophylaxis, Preoperative (Off-label use)

2.5 mg/kg IV/IM within 60 min piror to surgical incision or without antibiotics; procedure dependent  

Dose is based on actual body weight unless >20% above ideal body weight; then dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW- IBW)

Dosage Modifications

GFR>50 mL/min/1.73m²: No dosage adjustment necessary

GFR 30-50 mL/min/1.73m²: Administer q12-18hr

GFR 10-29 mL/min/1.73m²: Administer q18-24hr

GFR <10 mL/min/1.73m² Administer q48-72hr

Intermitent hemodialysis: 2 mg/kg/dose; redose as indicated by serum concentration

Peritoneal dialysis: 2 mg/kg/dose; redose as indicated by serum concentration

Continuous renal replacement therapy: 2-2.5 mg/kg/dose q12-24hr; monitor serum concentration  

Dosing Considerations

Monitor peak (4-12 mg/L) and trough (1-2 mg/L)

Monitor nephrotoxicity, neurotoxicity, and ototoxicity; assess at beginning of therapy and throughout

Individualization critical due to low therapeutic index

Use ideal body weight for mg/kg/dose, except in neonates (in whom actual body weight should be used)

Bacterial organisms causing susceptible infections

• Pseudomonas aeruginosa
• Proteus species (indole-positive and indole-negative)
• Escherichia coli
• Klebsiella-Enterobacter-Serratia species
• Citrobacter species
• Staphylococcus species (coagulase-positive and coagulase-negative)